EP0149297B1 - Procédé pour préparation de 3H-phénothiazine-3-ones - Google Patents
Procédé pour préparation de 3H-phénothiazine-3-ones Download PDFInfo
- Publication number
- EP0149297B1 EP0149297B1 EP19840304476 EP84304476A EP0149297B1 EP 0149297 B1 EP0149297 B1 EP 0149297B1 EP 19840304476 EP19840304476 EP 19840304476 EP 84304476 A EP84304476 A EP 84304476A EP 0149297 B1 EP0149297 B1 EP 0149297B1
- Authority
- EP
- European Patent Office
- Prior art keywords
- preparing
- phenothiazin
- reaction
- quinone
- methanol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- 238000004519 manufacturing process Methods 0.000 title 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 24
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 15
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 9
- 238000006243 chemical reaction Methods 0.000 claims description 7
- YKGCCFHSXQHWIG-UHFFFAOYSA-N phenothiazin-3-one Chemical compound C1=CC=C2SC3=CC(=O)C=CC3=NC2=C1 YKGCCFHSXQHWIG-UHFFFAOYSA-N 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 5
- 239000002798 polar solvent Substances 0.000 claims description 5
- FOIBSEIKXGLOJE-UHFFFAOYSA-N 2,7-dimethoxyphenothiazin-3-one Chemical compound C1=C(OC)C(=O)C=C2SC3=CC(OC)=CC=C3N=C21 FOIBSEIKXGLOJE-UHFFFAOYSA-N 0.000 claims description 4
- ZJKWJHONFFKJHG-UHFFFAOYSA-N 2-Methoxy-1,4-benzoquinone Chemical compound COC1=CC(=O)C=CC1=O ZJKWJHONFFKJHG-UHFFFAOYSA-N 0.000 claims description 4
- QHALDOSHHZPRRB-UHFFFAOYSA-N 2-amino-5-methoxybenzenethiol Chemical compound COC1=CC=C(N)C(S)=C1 QHALDOSHHZPRRB-UHFFFAOYSA-N 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 3
- VRVRGVPWCUEOGV-UHFFFAOYSA-N 2-aminothiophenol Chemical compound NC1=CC=CC=C1S VRVRGVPWCUEOGV-UHFFFAOYSA-N 0.000 claims description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- 150000001875 compounds Chemical class 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 2
- KZHGPDSVHSDCMX-UHFFFAOYSA-N 6-methoxy-1,3-benzothiazol-2-amine Chemical compound COC1=CC=C2N=C(N)SC2=C1 KZHGPDSVHSDCMX-UHFFFAOYSA-N 0.000 description 1
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000007822 coupling agent Substances 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 1
- FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 description 1
- 235000012141 vanillin Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C50/00—Quinones
- C07C50/26—Quinones containing groups having oxygen atoms singly bound to carbon atoms
- C07C50/28—Quinones containing groups having oxygen atoms singly bound to carbon atoms with monocyclic quinoid structure
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D279/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one sulfur atom as the only ring hetero atoms
- C07D279/10—1,4-Thiazines; Hydrogenated 1,4-thiazines
- C07D279/14—1,4-Thiazines; Hydrogenated 1,4-thiazines condensed with carbocyclic rings or ring systems
- C07D279/18—[b, e]-condensed with two six-membered rings
Definitions
- the present invention involves the preparation of 3H-phenothiazin-3-ones.
- the present invention provides a method for preparing 3H-phenothiazine-3-one comprising the reaction of 1 mole of o-mercaptoaniline with 2 moles of quinone in a polar solvent at a temperature in the range from -10°C to ambient.
- the reaction requires 2 moles of quinone B per mole of aniline A.
- the reaction is readily carried out at room temperature, but temperatures as low as -10° are suitable. No catalyst or coupling agent is required.
- Any suitable polar solvent may be used. It is advantageous to use a solvent which will dissolve the A, Band D components of the reaction and in which C is substantially insoluble, thus permitting direct recovery of substantially pure C.
- Useful preferred solvents are lower alkanols, acetic acid, and mixtures of lower alkanols or acetic acid with water.
- Vanillin (2.432 kg) was added to a solution of sodium hydroxide (640 g) in water (8 I) and cooled to 10°C with an ice-bath. Then a solution of hydrogen peroxide (30%) (2.4 1) was added at a rate to keep the temperature of the action mixture below 30°C. After the addition had been completed (about 2 hours), the reaction mixture was added over a period of 3 hours to a suspension of sodium periodate (880 g) in water (4 1) and acetic acid (640 ml) cooled with an ice-bath to 10°C (the temperature of the reaction mixture was kept below 35°C). The precipitate was filtered, washed with cold water followed by ethanol/hexane (1:1) mixture and air-dried to afford the title compound (1.9 kg), m.p. 144 ⁇ 147°C.
- Some advantages of the present process over the prior process are that (1) it utilizes a simple readily available cheap quinone, namely, quinone itself or a derivative thereof, (2) it can be carried out at room temperature and yet afford a high yield and (3) the byproduct hydroquinone can be easily oxidized and recirculated for use in the process.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
Claims (4)
1. Procédé pour la préparation de la 3H-phénothiazine-3-one qui comprend la réaction d'une mole d'o-mercaptoaniline avec 2 moles de quinone, dans un solvant polaire à une température comprise dans la plage de -10°C à la température ambiante.
2. Procédé pour la préparation de la 2,7-diméthoxy-3H-phénothiazine-3-one qui comprend la réaction d'une mole de 2-amino-5-méthoxy-thiophénol avec 2 moles de 2-méthoxy-p-benzoquinone dans un solvant polaire à la température ambiante.
3. Procédé selon la revendication 1 ou 2, qui est effectué à la température ambiante.
4. Procédé selon l'une quelconque des revendications précédentes, dans lequel le solvant est le méthanol, l'éthanol, l'acide acétique ou un mélange d'un ou plusieurs d'entre eux avec l'eau.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US56526983A | 1983-12-27 | 1983-12-27 | |
| US565269 | 1983-12-27 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EP0149297A1 EP0149297A1 (fr) | 1985-07-24 |
| EP0149297B1 true EP0149297B1 (fr) | 1987-11-25 |
Family
ID=24257875
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP19840304476 Expired EP0149297B1 (fr) | 1983-12-27 | 1984-06-29 | Procédé pour préparation de 3H-phénothiazine-3-ones |
Country Status (4)
| Country | Link |
|---|---|
| EP (1) | EP0149297B1 (fr) |
| JP (1) | JPS60139680A (fr) |
| CA (1) | CA1238323A (fr) |
| DE (1) | DE3467756D1 (fr) |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3229122A1 (de) * | 1982-08-04 | 1984-02-09 | Bayer Ag, 5090 Leverkusen | Anellierte 4h-1,4-benzothiazine, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel |
-
1984
- 1984-06-29 EP EP19840304476 patent/EP0149297B1/fr not_active Expired
- 1984-06-29 JP JP13341984A patent/JPS60139680A/ja active Pending
- 1984-06-29 DE DE8484304476T patent/DE3467756D1/de not_active Expired
- 1984-10-16 CA CA000465559A patent/CA1238323A/fr not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| EP0149297A1 (fr) | 1985-07-24 |
| CA1238323A (fr) | 1988-06-21 |
| JPS60139680A (ja) | 1985-07-24 |
| DE3467756D1 (en) | 1988-01-07 |
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Legal Events
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|---|---|---|---|
| PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
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| ITCL | It: translation for ep claims filed |
Representative=s name: SOCIETA' ITALIANA BREVETTI S.P.A. |
|
| 17P | Request for examination filed |
Effective date: 19851206 |
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| 17Q | First examination report despatched |
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| GRAA | (expected) grant |
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